1. Field of the Invention
The invention relates generally to photodynamic therapy and in particular to selective photoactivation of a commonly used drug.
2. Invention Disclosure Statement
Drug treatments are used in the treatment of a variety of illnesses. The problem with conventional treatments is their lack of selectivity. Drugs administered systemically are active in areas of the body where treatment is not needed. As a result, negative effects of the drug can be present in those areas. Side effects and their suppression have become an important aspect of developing useful and successful drugs. Drug delivery systems that allow selective activation of a drug only in the areas where the drug""s activity is needed would therefore be beneficial.
For example, U.S. Pat. No. 5,482,719 describes a drug delivery system in which a drug is combined with a photosensitive element. In this form, the drug is inactive. However, once the photosensitive element is cleaved off, by irradiation, the drug is released in an active form for treatment. The invention however, has limitations. For example, the drug compound described is complexed with a photosensitive macromolecule. The dimensions of this complex prevent it from migrating throughout the body. Therefore, wherever the complex is administered it will remain there localized for the duration of the treatment. This implies that for a given treatment, the practitioner must separately administer the complex to each area requiring treatment. This process is time consuming and becomes less practical with a greater number of treatment sites. What is needed is an activatible drug complex that has high selectivity yet can migrate throughout many areas of the body.
U.S. Pat. No. 5,277,913 describes a drug delivery system in which the drug is encapsulated in a liposome. Through irradiation or pH changes, the liposome xe2x80x98membranexe2x80x99 is ruptured and the drug contents released. The system providing for the drug delivery and release is complex and therefore problems can arise with its consistency of response. First, the release of the drug is triggered by irradiation or pH changes that effect a photosensitizer. The photosensitizer in turn produces a compound that will cleave a specific entity in the liposome xe2x80x98membranexe2x80x99. As a result, the xe2x80x98membrane xe2x80x99 opens and the liposome contents are allowed to xe2x80x98spillxe2x80x99 from the cavity. Having an indirect pathway to xe2x80x98membrane xe2x80x99 cleavage and drug dispersal leads to a variable and inconsistent treatment. Second, although the drug-release can be initiated through irradiation, the delivery system is also temperature and pH dependant. Both of these factors can vary depending on the part of the body receiving treatment. Therefore where multiple sites are involved, different sites may receive different drug doses for the same treatment. Further at temperatures lower than normal body temperature (37xc2x0 C.), the percentage of drug release by the liposomes decreases to the point where at 15xc2x0 C. the release drops to below 15%. This effect makes the invention inapplicable to topical drug applications where skin surface and surrounding environmental temperatures are often too low for an effective release.
Several patents exist that describe the use of photoactivatible fullerene compounds for various applications. Fullerenes are unique spherical structures formed from a specific number of carbon atoms (the number of carbon atoms can vary, in a fixed pattern, depending on the type of fullerene formed). A photosensistive or photoresponsive element can be added directly to the fullerene structure to make it responsive to applications of radiation. When radiation is applied to a xe2x80x98photosensitizedxe2x80x99 fullerene, it causes the fullerene structure to change and as a result xe2x80x98breaks openxe2x80x99 the spherical arrangement.
U.S. Pat. No. 5,561,026 as representative of a group of patents describing photoactivation and fullerenes, discloses an invention whereby a photosensitive group is added to the fullerene molecule to xe2x80x98photosensitivexe2x80x99 it. The invention disclosed however describes photoactivatible fullerenes for use as part of an overall photoactivatible or photosensitive material. The invention pertains solely to fullerene molecules used in aggregate comprising a layer or a coating of photosensitive materials. The invention does not suggest or imply using a photoactivatible fullerene as a delivery xe2x80x98vehiclexe2x80x99.
The present invention relates to using a photoactivatible fullerene as a delivery vehicle to selectively deliver drugs to a treatment site.
It is an aim of the present invention to provide a system for the activation of commonly used drugs with laser radiation whereby the drug compound is selectively activated only in the areas requiring treatment, thereby preventing exposure of non-treatment areas to potentially harmful side effects of the drug.
It is another aim of the present invention to complex the desired drug with a photoactivatible compound such as a xe2x80x98photosensitizedxe2x80x99 fullerene such that separation of the drug from the activation complex will activate the drug.
It is a further aim of the present invention to encapsulate the drug in a photoactivatible fullerene cage such that specifically applied radiation will alter the fullerene structure and release the drug.
Still another aim of the present invention is to attach a photoactivatible fullerene molecule to a commonly used drug such that the photoactivatible component of the fullerene molecule is bonded to the drug, and when irradiated will release the drug and thereby activate it.
Yet another aim of the present invention is to have a non-activated drug compound remain inactive and to be harmlessly removed or passed from the body.
Briefly stated, a device and method are presented wherein a common drug for a particular treatment is given to the patient in an inactive form. The drug can be administered systemically or topically. The activity of the drug is regulated by photoactivatible fullerene molecules to which the drug is complexed. When the drug is encapsulated in or attached to the photoactivatible fullerene molecule, it is inactive. When the inactive drug complex is subjected to selective irradiation however, the complex is broken and the drug is released in an active form. Treatment can be administered over a wide range of body areas, both internally and externally. The selectivity allows the drug in non-treatment areas to remain inactive, and then be removed or passed harmlessly from the body. The present invention facilitates drug treatment administration by allowing very specific treatment while minimizing the side effects.
The above, and other objects, features and advantages of the present invention will become apparent from the following description read in conjunction with the accompanying drawings.